Parkin Gene Alterations in Hepatocellular Carcinoma

Fang Wang, Stacy Denison, Jin Ping Lai, Leslie A. Philips, Damien Montoya, Norman Kock, Birgitt Schüle, Christine Klein, Vijayalakshmi Shridhar, Lewis Rowland Roberts, David I Smith

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The Parkin gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor-suppressor genes that are within CFS regions, we were interested in characterizing Parkin gene alterations and their possible association with cancer. After analyzing 50 cancer-derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC/PRF/5, had a detectable homozygous deletion encompassing exon 3, Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of Parkin exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of Parkin exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. Parkin gene-transfected PLC5 and Hep3B cells grew more slowly than vector-only transfectants and also showed increased sensitivity to apoptosis induced by cell-cycle inhibitors. Therefore, we suggest that Parkin may be involved in tumor suppression and that the loss of Parkin contributes to the development of hepatocarcinoma.

Original languageEnglish (US)
Pages (from-to)85-96
Number of pages12
JournalGenes Chromosomes and Cancer
Volume40
Issue number2
DOIs
StatePublished - Jun 2004

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Hepatocellular Carcinoma
Cell Line
Exons
Genes
Neoplasms
Tumor Suppressor Genes
Fluorescence In Situ Hybridization
Cell Cycle
Apoptosis
Breast Neoplasms
Polymerase Chain Reaction
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Wang, F., Denison, S., Lai, J. P., Philips, L. A., Montoya, D., Kock, N., ... Smith, D. I. (2004). Parkin Gene Alterations in Hepatocellular Carcinoma. Genes Chromosomes and Cancer, 40(2), 85-96. https://doi.org/10.1002/gcc.20020

Parkin Gene Alterations in Hepatocellular Carcinoma. / Wang, Fang; Denison, Stacy; Lai, Jin Ping; Philips, Leslie A.; Montoya, Damien; Kock, Norman; Schüle, Birgitt; Klein, Christine; Shridhar, Vijayalakshmi; Roberts, Lewis Rowland; Smith, David I.

In: Genes Chromosomes and Cancer, Vol. 40, No. 2, 06.2004, p. 85-96.

Research output: Contribution to journalArticle

Wang, F, Denison, S, Lai, JP, Philips, LA, Montoya, D, Kock, N, Schüle, B, Klein, C, Shridhar, V, Roberts, LR & Smith, DI 2004, 'Parkin Gene Alterations in Hepatocellular Carcinoma', Genes Chromosomes and Cancer, vol. 40, no. 2, pp. 85-96. https://doi.org/10.1002/gcc.20020
Wang F, Denison S, Lai JP, Philips LA, Montoya D, Kock N et al. Parkin Gene Alterations in Hepatocellular Carcinoma. Genes Chromosomes and Cancer. 2004 Jun;40(2):85-96. https://doi.org/10.1002/gcc.20020
Wang, Fang ; Denison, Stacy ; Lai, Jin Ping ; Philips, Leslie A. ; Montoya, Damien ; Kock, Norman ; Schüle, Birgitt ; Klein, Christine ; Shridhar, Vijayalakshmi ; Roberts, Lewis Rowland ; Smith, David I. / Parkin Gene Alterations in Hepatocellular Carcinoma. In: Genes Chromosomes and Cancer. 2004 ; Vol. 40, No. 2. pp. 85-96.
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